The purpose of this project is to improve our understanding of the role of protein synthesis in focal epilepsy and metabolic brain disease. (1) We will develop semi-micro methods for studying cerebral protein synthesis in vivo and use them to investigate changes in protein synthesis that occur in the epileptic focus induced by penicillin, aluminium, cobalt, or kindling. We will also investigate possible relationships between focal changes in protein synthesis and the occurrrence of possible relationships between focal changes in protein synthesis and the occurrence of (a) post-ictal (Todd's) paralysis; (b) chronic histological changes in the epileptic focus; (c) changes in energy metabolism and blood-brain barrier observed in focal epilepsy. (2) We will analyze the effects of inhibitors of protein synthesis on the formation of Goddard's kindling phenomenon in vivo. (3) We will attempt to achieve kindling in isolated frog brain and in rodent olfactory bulb in vitro. If successful, we will use this in vitro model for further studies of the effects on kindling of (1) protein synthesis inhibitors; (2) putative transmitter agonists and antagonists. (4) The methods developed for the study of seizures will be used to investigate general and regional brain protein synthesis in aging. The brain is an excellent organ in which to study aging because it is one of the primary sites of aging, it is immunologically privileged, and the age of most brain cells is close to the age of the organism. (5) The same methodology will be applied to the study of chronic porto-caval encephalopathy in rats. Possible changes in brain protein synthesis will be correlated with blood ammonia levels and with the production of Alzheimer Type II cells. The possible role of alpha-ketoglutaramate will also be investigated. (6) We will study the effects on brain protein synthesis of chronic alcohol ingestion in rodents and primates, using paired feeding methods to maintain comparable nutritional status in alcohol-ingesting and control animals.